Pub Date : 2026-06-01Epub Date: 2026-02-09DOI: 10.1016/j.jad.2026.121370
Ahsan Aziz Sarkar , Md Faruq Alam , Helal Uddin Ahmed , Mohammad Tariqul Alam , Niaz Mohammad Khan
Background
Depressive disorders are among the leading causes of disability worldwide. Cultural variations in symptom presentation and the wide treatment gap in low- and middle-income countries underscore the need for country-specific data.
Methods
A nationally representative household survey was conducted among Bangladeshi adults. Participants were first screened with the Self-Reporting Questionnaire (SRQ), and those screening positive underwent face-to-face clinical interviews with trained psychiatrists. Diagnoses were made using the DSM-5 criteria.
Results
A total of 7270 adults completed all study procedures. The weighted current prevalence of depressive disorders was 5.2% (95% CI: 4.5–6.0), comprising 3.9% with major depressive disorder and 1.3% with persistent depressive disorder, based on DSM-5 criteria assessed through psychiatric interviews. Higher prevalence was observed among older adults aged ≥60 years (aOR = 1.55), females (aOR = 1.53), individuals with lower education (aOR = 1.68), divorced, separated, or widowed (aOR = 2.09), unemployed (aOR = 2.87), and those with a family history of mental illness (aOR = 3.58) or suicidal behavior (aOR = 2.17). Among affected individuals, somatic symptoms were more commonly reported than affective or cognitive symptoms of depression. Despite this considerable burden, the treatment gap remained high, with only 4.1% seeking professional help.
Conclusion
Depression imposes a substantial burden in Bangladesh. The findings highlight the need for enhanced awareness and mental health literacy programs to address the treatment gap. Findings indicate that certain physical complaints may reflect underlying depression and therefore warrant routine depression screening; this highlights the importance of culturally sensitive screening instruments.
{"title":"Prevalence, symptom profile, associated factors, and treatment gap of depressive disorders among adults: Findings from a nationwide household survey in Bangladesh","authors":"Ahsan Aziz Sarkar , Md Faruq Alam , Helal Uddin Ahmed , Mohammad Tariqul Alam , Niaz Mohammad Khan","doi":"10.1016/j.jad.2026.121370","DOIUrl":"10.1016/j.jad.2026.121370","url":null,"abstract":"<div><h3>Background</h3><div>Depressive disorders are among the leading causes of disability worldwide. Cultural variations in symptom presentation and the wide treatment gap in low- and middle-income countries underscore the need for country-specific data.</div></div><div><h3>Methods</h3><div>A nationally representative household survey was conducted among Bangladeshi adults. Participants were first screened with the Self-Reporting Questionnaire (SRQ), and those screening positive underwent face-to-face clinical interviews with trained psychiatrists. Diagnoses were made using the DSM-5 criteria.</div></div><div><h3>Results</h3><div>A total of 7270 adults completed all study procedures. The weighted current prevalence of depressive disorders was 5.2% (95% CI: 4.5–6.0), comprising 3.9% with major depressive disorder and 1.3% with persistent depressive disorder, based on DSM-5 criteria assessed through psychiatric interviews. Higher prevalence was observed among older adults aged ≥60 years (aOR = 1.55), females (aOR = 1.53), individuals with lower education (aOR = 1.68), divorced, separated, or widowed (aOR = 2.09), unemployed (aOR = 2.87), and those with a family history of mental illness (aOR = 3.58) or suicidal behavior (aOR = 2.17). Among affected individuals, somatic symptoms were more commonly reported than affective or cognitive symptoms of depression. Despite this considerable burden, the treatment gap remained high, with only 4.1% seeking professional help.</div></div><div><h3>Conclusion</h3><div>Depression imposes a substantial burden in Bangladesh. The findings highlight the need for enhanced awareness and mental health literacy programs to address the treatment gap. Findings indicate that certain physical complaints may reflect underlying depression and therefore warrant routine depression screening; this highlights the importance of culturally sensitive screening instruments.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121370"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-09DOI: 10.1016/j.jad.2026.121327
Ling Zhu , Qiao Mao , Zhixiong Luo , Bin Chen , Yong Zhang , Xiaowei Lu , Ping Liu , Jiawu Ji , Xiaoping Wang , Kesheng Wang , Xinghua Pan , Yuping Cao , Na Liu , Jianming Zheng , Fan Wang , Kebing Yang , Fude Yang , Zongyang Yu , Jia Hu , Jennifer Luo , Xiaoyun Guo
Objectives
P2RX7 has been implicated in bipolar disorder, major depressive disorder, schizophrenia, anxiety disorders, Alzheimer's disease, and Parkinson's disease. However, the specificity and comparability of these associations remain unclear. This study aimed to systematically evaluate multiple neuropsychiatric disorders to identify those most robustly associated with P2RX7.
Methods
We analyzed 1861 imputed SNPs spanning the P2RX7 gene in 1,087,925 individuals from 72 independent cohorts across 18 neuropsychiatric disorders. SNP-disease associations were assessed within each cohort, followed by meta-analysis and false discovery rate (FDR) correction to identify significant disease-risk variants. P2RX7 mRNA and protein expression across tissues or cells was characterized. Functional analyses evaluated the regulatory effects of disease-associated SNPs on P2RX7 mRNA expression, subcortical gray matter volumes (GMVs), cortical surface area (SA), and cortical thickness (TH).
Results
Bipolar disorder showed the strongest association with P2RX7 variants in European Americans (EAs) (4.0 × 10−8 ≤ p ≤ 0.004; 3.8 × 10−5 ≤ q ≤ 0.05), followed by schizophrenia in EAs (8.9 × 10−6 ≤ p ≤ 2.6 × 10−4; 9.4 × 10−3 ≤ q ≤ 0.043) and Chinese populations (2.1 × 10−5 ≤ p ≤ 1.7 × 10−3; 6.8 × 10−3 ≤ q ≤ 0.049), and major depression in both EAs (p = 4.1 × 10−5; q = 0.030) and Chinese (4.3 × 10−5 ≤ p ≤ 0.009; 6.1 × 10−3 ≤ q ≤ 0.046). The significance of most associations and their relative ranking across disorders was maintained in the trans-ancestry meta-analysis. Expression analysis revealed that P2RX7 mRNA and protein expression were abundant in the brain, glial cells and macrophages. Approximately half of the disease-associated SNPs significantly influenced P2RX7 mRNA expression in nine brain regions (1.0 × 10−7 ≤ p ≤ 0.047) and altered GMV, SA, and TH of seven brain regions (1.9 × 10−4 ≤ p ≤ 3.4 × 10−3).
Conclusion
P2RX7 is most consistently and specifically associated with bipolar disorder, schizophrenia, and major depression, supported by both statistical and biological evidence.
{"title":"Phenome-wide association study of P2RX7 identifies schizophrenia and mood disorders as primary associated phenotypes","authors":"Ling Zhu , Qiao Mao , Zhixiong Luo , Bin Chen , Yong Zhang , Xiaowei Lu , Ping Liu , Jiawu Ji , Xiaoping Wang , Kesheng Wang , Xinghua Pan , Yuping Cao , Na Liu , Jianming Zheng , Fan Wang , Kebing Yang , Fude Yang , Zongyang Yu , Jia Hu , Jennifer Luo , Xiaoyun Guo","doi":"10.1016/j.jad.2026.121327","DOIUrl":"10.1016/j.jad.2026.121327","url":null,"abstract":"<div><h3>Objectives</h3><div><em>P2RX7</em> has been implicated in bipolar disorder, major depressive disorder, schizophrenia, anxiety disorders, Alzheimer's disease, and Parkinson's disease. However, the specificity and comparability of these associations remain unclear. This study aimed to systematically evaluate multiple neuropsychiatric disorders to identify those most robustly associated with <em>P2RX7</em>.</div></div><div><h3>Methods</h3><div>We analyzed 1861 imputed SNPs spanning the <em>P2RX7</em> gene in 1,087,925 individuals from 72 independent cohorts across 18 neuropsychiatric disorders. SNP-disease associations were assessed within each cohort, followed by meta-analysis and false discovery rate (FDR) correction to identify significant disease-risk variants. <em>P2RX7</em> mRNA and protein expression across tissues or cells was characterized. Functional analyses evaluated the regulatory effects of disease-associated SNPs on <em>P2RX7</em> mRNA expression, subcortical gray matter volumes (GMVs), cortical surface area (SA), and cortical thickness (TH).</div></div><div><h3>Results</h3><div>Bipolar disorder showed the strongest association with <em>P2RX7</em> variants in European Americans (EAs) (4.0 × 10<sup>−8</sup> ≤ <em>p</em> ≤ 0.004; 3.8 × 10<sup>−5</sup> ≤ q ≤ 0.05), followed by schizophrenia in EAs (8.9 × 10<sup>−6</sup> ≤ <em>p</em> ≤ 2.6 × 10<sup>−4</sup>; 9.4 × 10<sup>−3</sup> ≤ q ≤ 0.043) and Chinese populations (2.1 × 10<sup>−5</sup> ≤ <em>p</em> ≤ 1.7 × 10<sup>−3</sup>; 6.8 × 10<sup>−3</sup> ≤ q ≤ 0.049), and major depression in both EAs (<em>p</em> = 4.1 × 10<sup>−5</sup>; q = 0.030) and Chinese (4.3 × 10<sup>−5</sup> ≤ <em>p</em> ≤ 0.009; 6.1 × 10<sup>−3</sup> ≤ q ≤ 0.046). The significance of most associations and their relative ranking across disorders was maintained in the trans-ancestry meta-analysis. Expression analysis revealed that <em>P2RX7</em> mRNA and protein expression were abundant in the brain, glial cells and macrophages. Approximately half of the disease-associated SNPs significantly influenced <em>P2RX7</em> mRNA expression in nine brain regions (1.0 × 10<sup>−7</sup> ≤ <em>p</em> ≤ 0.047) and altered GMV, SA, and TH of seven brain regions (1.9 × 10<sup>−4</sup> ≤ <em>p</em> ≤ 3.4 × 10<sup>−3</sup>).</div></div><div><h3>Conclusion</h3><div><em>P2RX7</em> is most consistently and specifically associated with bipolar disorder, schizophrenia, and major depression, supported by both statistical and biological evidence.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121327"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-09DOI: 10.1016/j.jad.2026.121367
Pauline Rivart , Saied Ibrahim , Lana Bojanić , Pauline Turnbull , Cathryn Rodway , Louis Appleby , Nav Kapur , Isabelle M. Hunt
Background
Previous research has highlighted the importance of surveillance of suicide methods to identify emerging patterns and to support prevention strategies. However, research on methods in clinical populations is limited. We aimed to investigate trends in suicide methods by people who had been in contact with mental health services in the 12 months before death.
Method
Data were collected as part of the National Confidential Inquiry into Suicide and Safety in Mental Health. We examined method-specific trends among psychiatric patients in the UK who died by suicide between 2000 and 2022 using an exploratory joinpoint regression analysis.
Findings
Hanging/strangulation increased by 43.0% over the study period, or 1.9% per year, while cutting/stabbing increased by 88.9%, or 4.2% per year. Deaths by self-poisoning, drowning and gas inhalation decreased by 1.7%, 2.3% and 4.6% every year respectively. No significant trends were identified for deaths by jumping/multiple injuries. No changes overall were identified in the last three years of the study, including during the COVID-19 pandemic.
Discussion
The increase in patient suicide deaths by hanging/strangulation is of concern. Attention should be paid to the steady increase in deaths by cutting/stabbing. Our findings support the need for surveillance, including real-time surveillance, of emerging methods and continued efforts towards means restriction.
{"title":"Trends in methods of suicide among mental health patients between 2000 and 2022 in the UK: A joinpoint regression analysis","authors":"Pauline Rivart , Saied Ibrahim , Lana Bojanić , Pauline Turnbull , Cathryn Rodway , Louis Appleby , Nav Kapur , Isabelle M. Hunt","doi":"10.1016/j.jad.2026.121367","DOIUrl":"10.1016/j.jad.2026.121367","url":null,"abstract":"<div><h3>Background</h3><div>Previous research has highlighted the importance of surveillance of suicide methods to identify emerging patterns and to support prevention strategies. However, research on methods in clinical populations is limited. We aimed to investigate trends in suicide methods by people who had been in contact with mental health services in the 12 months before death.</div></div><div><h3>Method</h3><div>Data were collected as part of the National Confidential Inquiry into Suicide and Safety in Mental Health. We examined method-specific trends among psychiatric patients in the UK who died by suicide between 2000 and 2022 using an exploratory joinpoint regression analysis.</div></div><div><h3>Findings</h3><div>Hanging/strangulation increased by 43.0% over the study period, or 1.9% per year, while cutting/stabbing increased by 88.9%, or 4.2% per year. Deaths by self-poisoning, drowning and gas inhalation decreased by 1.7%, 2.3% and 4.6% every year respectively. No significant trends were identified for deaths by jumping/multiple injuries. No changes overall were identified in the last three years of the study, including during the COVID-19 pandemic.</div></div><div><h3>Discussion</h3><div>The increase in patient suicide deaths by hanging/strangulation is of concern. Attention should be paid to the steady increase in deaths by cutting/stabbing. Our findings support the need for surveillance, including real-time surveillance, of emerging methods and continued efforts towards means restriction.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121367"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-04DOI: 10.1016/j.jad.2026.121346
Min Wu , Honghong Ren , Xin Wang , Huixue Xu , Zejun Li , Yueheng Liu , Manyun Li , Qiuxia Wu , Tieqiao Liu , Qianjin Wang
Background
Major depressive disorder (MDD) and Internet addiction (IA) are common and cause significant impairment, yet their relationship remains unclear. This study aims to explore the neurobiological mechanisms of comorbid MDD and IA and to inform clinical interventions.
Methods
This study recruited 141 first-episode, drug-naïve MDD patients (72 with IA, 69 without) and 61 healthy controls (HC). Clinical assessments included the Hamilton Depression Rating Scale (HAMD) and Internet Addiction Test (IAT). Resting-state fMRI data were acquired using a 3 T Siemens scanner, and fractional amplitude of low-frequency fluctuations (fALFF) was computed with the Data Processing Assistant for Resting-State fMRI (DPARSF) software. Statistical analyses involved ANOVA, MANCOVA, and partial correlation, with multiple comparisons corrected using the FDR and Bonferroni methods.
Results
Compared to HC group, both MDD + IA and MDD groups exhibited common elevations in fALFF within the left superior medial frontal gyrus and right superior frontal gyrus, alongside reductions in the right middle occipital gyrus. Concurrently, group-specific alterations were identified: MDD + IA had higher fALFF in the right inferior frontal gyrus triangular region, while MDD exhibited lower fALFF in the right postcentral gyrus and left inferior temporal gyrus. MDD + IA had significantly higher fALFF in the left inferior parietal lobule than MDD. Furthermore, fALFF in this region was positively correlated with IAT scores.
Conclusions
MDD with IA is associated with distinct neurological alterations in frontal and parietal regions. The left inferior parietal lobule may serve as a potential neurobiological marker for MDD comorbid with IA, providing a target for future interventions.
{"title":"The characteristics of fractional amplitude of low frequency fluctuation among first-episode and drug-naive individuals with depressive disorder combined with internet addiction","authors":"Min Wu , Honghong Ren , Xin Wang , Huixue Xu , Zejun Li , Yueheng Liu , Manyun Li , Qiuxia Wu , Tieqiao Liu , Qianjin Wang","doi":"10.1016/j.jad.2026.121346","DOIUrl":"10.1016/j.jad.2026.121346","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) and Internet addiction (IA) are common and cause significant impairment, yet their relationship remains unclear. This study aims to explore the neurobiological mechanisms of comorbid MDD and IA and to inform clinical interventions.</div></div><div><h3>Methods</h3><div>This study recruited 141 first-episode, drug-naïve MDD patients (72 with IA, 69 without) and 61 healthy controls (HC). Clinical assessments included the Hamilton Depression Rating Scale (HAMD) and Internet Addiction Test (IAT). Resting-state fMRI data were acquired using a 3 T Siemens scanner, and fractional amplitude of low-frequency fluctuations (fALFF) was computed with the Data Processing Assistant for Resting-State fMRI (DPARSF) software. Statistical analyses involved ANOVA, MANCOVA, and partial correlation, with multiple comparisons corrected using the FDR and Bonferroni methods.</div></div><div><h3>Results</h3><div>Compared to HC group, both MDD + IA and MDD groups exhibited common elevations in fALFF within the left superior medial frontal gyrus and right superior frontal gyrus, alongside reductions in the right middle occipital gyrus. Concurrently, group-specific alterations were identified: MDD + IA had higher fALFF in the right inferior frontal gyrus triangular region, while MDD exhibited lower fALFF in the right postcentral gyrus and left inferior temporal gyrus. MDD + IA had significantly higher fALFF in the left inferior parietal lobule than MDD. Furthermore, fALFF in this region was positively correlated with IAT scores.</div></div><div><h3>Conclusions</h3><div>MDD with IA is associated with distinct neurological alterations in frontal and parietal regions. The left inferior parietal lobule may serve as a potential neurobiological marker for MDD comorbid with IA, providing a target for future interventions.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121346"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-04DOI: 10.1016/j.jad.2026.121343
Isabell Int-Veen , Andreas J. Fallgatter , Ann-Christine Ehlis , David Rosenbaum
Understanding how brain activation relates to the content of our thoughts under stress is essential for linking cognitive processes to neural mechanisms. The Think Aloud Paradigm (TAP) offers a unique, real-time method to capture verbalized cognition, enabling researchers to assess the qualitative nature of ruminative thinking. In this study, the TAP was administered prior to and following the Trier Social Stress Test (TSST) to investigate whether verbalized ruminative thought content is associated with prefrontal hypoactivation during stress. Participants' transcripts were rated on four scales: (1) rehashing bad performance, (2) speculating about negative consequences, (3) focus on negative affect, and (4) reflection. Dichotomized change scores were used as group-level predictors of neural activation. Results showed that rehashing bad performance and speculating about negative consequences were significantly associated with differential activation patterns in the bilateral Inferior Frontal Gyrus (IFG) and left Dorsolateral Prefrontal Cortex (DLPFC). Interestingly, this association shows opposing patterns for each hemisphere: Specifically, participants who less frequently engage in rehashing bad performance and speculating about negative consequences show increased recruitment of the left IFG and left DLPFC under stress, whereas those who do show prefrontal hypoactivation. Participants who rehashed their poor performance further showed decreased activation in the right IFG over time, while those who did not showed no significant changes in the right IFG. These findings suggest that ruminative thought content, as captured through TAP, is associated with reduced prefrontal engagement during stress. Future research should investigate this relationship in clinical populations to evaluate its potential for diagnostic or intervention purposes.
{"title":"Neural correlates of verbalized cognition: Linking prefrontal activation under stress to the qualitative content of thought during rumination","authors":"Isabell Int-Veen , Andreas J. Fallgatter , Ann-Christine Ehlis , David Rosenbaum","doi":"10.1016/j.jad.2026.121343","DOIUrl":"10.1016/j.jad.2026.121343","url":null,"abstract":"<div><div>Understanding how brain activation relates to the content of our thoughts under stress is essential for linking cognitive processes to neural mechanisms. The Think Aloud Paradigm (TAP) offers a unique, real-time method to capture verbalized cognition, enabling researchers to assess the qualitative nature of ruminative thinking. In this study, the TAP was administered prior to and following the Trier Social Stress Test (TSST) to investigate whether verbalized ruminative thought content is associated with prefrontal hypoactivation during stress. Participants' transcripts were rated on four scales: (1) rehashing bad performance, (2) speculating about negative consequences, (3) focus on negative affect, and (4) reflection. Dichotomized change scores were used as group-level predictors of neural activation. Results showed that rehashing bad performance and speculating about negative consequences were significantly associated with differential activation patterns in the bilateral Inferior Frontal Gyrus (IFG) and left Dorsolateral Prefrontal Cortex (DLPFC). Interestingly, this association shows opposing patterns for each hemisphere: Specifically, participants who less frequently engage in rehashing bad performance and speculating about negative consequences show increased recruitment of the left IFG and left DLPFC under stress, whereas those who do show prefrontal hypoactivation. Participants who rehashed their poor performance further showed decreased activation in the right IFG over time, while those who did not showed no significant changes in the right IFG. These findings suggest that ruminative thought content, as captured through TAP, is associated with reduced prefrontal engagement during stress. Future research should investigate this relationship in clinical populations to evaluate its potential for diagnostic or intervention purposes.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121343"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-10DOI: 10.1016/j.jad.2026.121379
Mingqi Wang , Benke Xu , Chenxi Zhang , Naixue Cui , Guoxiao Sun
Background
eHealth has received growing attention as a promising and accessible paradigm for delivering mental health services among older adults with subthreshold depression (sD).
Objective
This study aimed to comprehensively synthesize effects of eHealth interventions on depressive symptoms, anxiety symptoms, and quality of life (QoL) in older adults with sD, as well as potential moderators that influence the effects.
Methods
A comprehensive search of five databases (MEDLINE, Embase, Web of Science, PsycINFO, and Scopus) was conducted to identify relevant randomized controlled trials. The primary outcome (depressive symptoms) and secondary outcomes (anxiety symptoms and QoL) were synthesized using random-effects meta-analysis models. Subgroup analyses and meta-regressions were used to identify factors associated with the intervention effects on primary outcome.
Results
32 trials (3973 participants) were included. eHealth interventions were effective in improving depressive symptoms (g = −0.35, 95% CI −0.45 to −0.24), anxiety symptoms (g = −0.47, 95% CI −0.73 to −0.20), and QoL (g = 0.21, 95% CI 0.08 to 0.34) in older adults with sD. Subgroup analyses revealed that virtual reality-based interventions were the most effective eHealth component (g = −1.08, 95% CI −1.59 to −0.56). Greater improvements in depressive symptoms were also observed in participants without comorbid conditions, receiving single-component intervention, or undergoing shorter intervention durations. Sensitivity analyses confirmed the reliability of these results.
Conclusion
eHealth interventions are effective in improving mental health and QoL in older adults with sD. Further high-quality trials should evaluate their sustained effects and validate the optimal delivery formats for older adults with sD.
背景：电子健康作为一种有前途和可获得的范式，为患有阈下抑郁症（sD）的老年人提供心理健康服务，已受到越来越多的关注。目的：本研究旨在全面综合eHealth干预对老年sD患者抑郁症状、焦虑症状和生活质量（QoL）的影响，以及影响这些影响的潜在调节因子。方法：综合检索MEDLINE、Embase、Web of Science、PsycINFO、Scopus 5个数据库，筛选相关随机对照试验。主要结局（抑郁症状）和次要结局（焦虑症状和生活质量）采用随机效应荟萃分析模型进行综合。采用亚组分析和元回归来确定与干预对主要结局的影响相关的因素。结果：纳入32项试验（3973名受试者）。电子健康干预在改善老年sD患者的抑郁症状（g = -0.35,95% CI -0.45至-0.24）、焦虑症状（g = -0.47,95% CI -0.73至-0.20）和生活质量（g = 0.21,95% CI 0.08至0.34）方面是有效的。亚组分析显示，基于虚拟现实的干预措施是最有效的电子健康成分（g = -1.08,95% CI -1.59至-0.56）。在没有合并症、接受单一成分干预或接受较短干预时间的参与者中，也观察到抑郁症状的更大改善。敏感性分析证实了这些结果的可靠性。结论：电子健康干预能有效改善老年sD患者的心理健康和生活质量。进一步的高质量试验应评估其持续效果，并验证老年sD患者的最佳给药方式。
{"title":"The effect of eHealth interventions on mental health and quality of life in older adults with subthreshold depression: A systematic review and meta-analysis","authors":"Mingqi Wang , Benke Xu , Chenxi Zhang , Naixue Cui , Guoxiao Sun","doi":"10.1016/j.jad.2026.121379","DOIUrl":"10.1016/j.jad.2026.121379","url":null,"abstract":"<div><h3>Background</h3><div>eHealth has received growing attention as a promising and accessible paradigm for delivering mental health services among older adults with subthreshold depression (sD).</div></div><div><h3>Objective</h3><div>This study aimed to comprehensively synthesize effects of eHealth interventions on depressive symptoms, anxiety symptoms, and quality of life (QoL) in older adults with sD, as well as potential moderators that influence the effects.</div></div><div><h3>Methods</h3><div>A comprehensive search of five databases (MEDLINE, Embase, Web of Science, PsycINFO, and Scopus) was conducted to identify relevant randomized controlled trials. The primary outcome (depressive symptoms) and secondary outcomes (anxiety symptoms and QoL) were synthesized using random-effects meta-analysis models. Subgroup analyses and meta-regressions were used to identify factors associated with the intervention effects on primary outcome.</div></div><div><h3>Results</h3><div>32 trials (3973 participants) were included. eHealth interventions were effective in improving depressive symptoms (g = −0.35, 95% CI −0.45 to −0.24), anxiety symptoms (g = −0.47, 95% CI −0.73 to −0.20), and QoL (g = 0.21, 95% CI 0.08 to 0.34) in older adults with sD. Subgroup analyses revealed that virtual reality-based interventions were the most effective eHealth component (g = −1.08, 95% CI −1.59 to −0.56). Greater improvements in depressive symptoms were also observed in participants without comorbid conditions, receiving single-component intervention, or undergoing shorter intervention durations. Sensitivity analyses confirmed the reliability of these results.</div></div><div><h3>Conclusion</h3><div>eHealth interventions are effective in improving mental health and QoL in older adults with sD. Further high-quality trials should evaluate their sustained effects and validate the optimal delivery formats for older adults with sD.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121379"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypothyroidism is linked to depression and several metabolic alterations, including insulin resistance, dyslipidemia, and oxidative stress. This study investigates the impact of hormones, autoimmunity, metabolic, and antioxidant indicators on the severity of depression in patients with hypothyroidism.
Methods
Forty-six patients with hypothyroidism and seventy-four with Hashimoto's thyroiditis participated in this study, along with sixty healthy controls. Patients were categorized based on the Hamilton Depression Rating Scale (≥ 17) into those with depression and those without. The enzyme-linked immunosorbent assay method was employed to evaluate blood insulin and selenoprotein P (SePP). Graphite furnace atomic absorption spectrophotometry was employed to quantify serum selenium concentrations. Serum zinc and lipid profile indicators were measured using spectrophotometry.
Results
Hypothyroidism and Hashimoto's thyroiditis are linked to increased atherogenicity, insulin resistance, and reduced antioxidant defenses, including selenium, SePP, and zinc. Both cohorts with thyroid dysfunctions demonstrate slight elevations in depressive symptoms. Individuals with hypothyroidism and heightened depressive symptoms demonstrated augmented insulin resistance, raised atherogenic indices, and markedly reduced levels of SePP relative to those with milder depressive symptoms. Elevated levels of thyroid-stimulating hormone and atherogenic index of plasma best predicted the severity of depression in hypothyroid patients.
Conclusions
The findings indicate that depression due to hypothyroidism is largely influenced by abnormalities in thyroid hormones, thyroid-stimulating hormone, metabolic pathways, and diminished antioxidant defenses. The observed results may be explained by the established impact of these hormones and biomarkers on cerebral functions, resulting in major depressive disorder.
{"title":"Neuro-immune, metabolic, and oxidative pathways in depression due to hypothyroidism and Hashimoto's thyroiditis","authors":"Sahira Qasim Al-Baldawi , Hussein Kadhem Al-Hakeim , Ikram Khémiri , Michael Maes","doi":"10.1016/j.jad.2026.121224","DOIUrl":"10.1016/j.jad.2026.121224","url":null,"abstract":"<div><h3>Background</h3><div>Hypothyroidism is linked to depression and several metabolic alterations, including insulin resistance, dyslipidemia, and oxidative stress. This study investigates the impact of hormones, autoimmunity, metabolic, and antioxidant indicators on the severity of depression in patients with hypothyroidism.</div></div><div><h3>Methods</h3><div>Forty-six patients with hypothyroidism and seventy-four with Hashimoto's thyroiditis participated in this study, along with sixty healthy controls. Patients were categorized based on the Hamilton Depression Rating Scale (≥ 17) into those with depression and those without. The enzyme-linked immunosorbent assay method was employed to evaluate blood insulin and selenoprotein P (SePP). Graphite furnace atomic absorption spectrophotometry was employed to quantify serum selenium concentrations. Serum zinc and lipid profile indicators were measured using spectrophotometry.</div></div><div><h3>Results</h3><div>Hypothyroidism and Hashimoto's thyroiditis are linked to increased atherogenicity, insulin resistance, and reduced antioxidant defenses, including selenium, SePP, and zinc. Both cohorts with thyroid dysfunctions demonstrate slight elevations in depressive symptoms. Individuals with hypothyroidism and heightened depressive symptoms demonstrated augmented insulin resistance, raised atherogenic indices, and markedly reduced levels of SePP relative to those with milder depressive symptoms. Elevated levels of thyroid-stimulating hormone and atherogenic index of plasma best predicted the severity of depression in hypothyroid patients.</div></div><div><h3>Conclusions</h3><div>The findings indicate that depression due to hypothyroidism is largely influenced by abnormalities in thyroid hormones, thyroid-stimulating hormone, metabolic pathways, and diminished antioxidant defenses. The observed results may be explained by the established impact of these hormones and biomarkers on cerebral functions, resulting in major depressive disorder.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121224"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-05DOI: 10.1016/j.jad.2026.121329
Hugo A.E. Morandini , Sjoerd B. Vos , Ranila Bhoyroo , Angela Jacques , Pradeep Rao
Background
ADHD has been associated with impaired central nervous dopaminergic pathways. Brain iron is an essential cofactor for the synthesis of dopamine and the substantia nigra (SN) is a significant pool of dopaminergic neurons playing a central role in the activity of the nigrostriatal pathway. The present study investigated SN iron content in children with ADHD, its relationship with ADHD symptom severity and cognitive performance.
Methods
Neuroimaging and phenotypical data were extracted from the Healthy Brain Network dataset. After initial screening, 54 medication-naïve children with ADHD and 44 neurotypical (NT) children (8–12 year) were included. ADHD symptom severity was extracted from the Child Behavior Checklist (CBCL) Parent report and working memory (WM) and inhibitory control scores from the National Institute of Health toolbox.
Results
A mixed between-within subjects ANOVA revealed no significant difference in SN iron content between medication-naïve children with ADHD and NT (partial eta squared = 0.001, p = .79). In the ADHD group, Spearman's correlation revealed a significant inverse relationship between left (r = −0.38; p < .01) and right (r = −0.33; p = .01) SN iron content and CBCL Attention Problems T score, while in the NT group left SN iron content significantly correlated with inhibitory control (r = 0.36; p = .02).
Conclusions
Although there was no difference in nigral iron content between both groups, higher SN iron content was associated with lower attention problems in children with ADHD and higher SN iron content was associated with better inhibitory control in NT children.
{"title":"Clinical and cognitive profile of nigral iron content in children with ADHD","authors":"Hugo A.E. Morandini , Sjoerd B. Vos , Ranila Bhoyroo , Angela Jacques , Pradeep Rao","doi":"10.1016/j.jad.2026.121329","DOIUrl":"10.1016/j.jad.2026.121329","url":null,"abstract":"<div><h3>Background</h3><div>ADHD has been associated with impaired central nervous dopaminergic pathways. Brain iron is an essential cofactor for the synthesis of dopamine and the substantia nigra (SN) is a significant pool of dopaminergic neurons playing a central role in the activity of the nigrostriatal pathway. The present study investigated SN iron content in children with ADHD, its relationship with ADHD symptom severity and cognitive performance.</div></div><div><h3>Methods</h3><div>Neuroimaging and phenotypical data were extracted from the Healthy Brain Network dataset. After initial screening, 54 medication-naïve children with ADHD and 44 neurotypical (NT) children (8–12 year) were included. ADHD symptom severity was extracted from the Child Behavior Checklist (CBCL) Parent report and working memory (WM) and inhibitory control scores from the National Institute of Health toolbox.</div></div><div><h3>Results</h3><div>A mixed between-within subjects ANOVA revealed no significant difference in SN iron content between medication-naïve children with ADHD and NT (partial eta squared = 0.001, <em>p</em> = .79). In the ADHD group, Spearman's correlation revealed a significant inverse relationship between left (<em>r</em> = −0.38; <em>p</em> < .01) and right (<em>r</em> = −0.33; <em>p</em> = .01) SN iron content and CBCL Attention Problems T score, while in the NT group left SN iron content significantly correlated with inhibitory control (<em>r</em> = 0.36; <em>p</em> = .02).</div></div><div><h3>Conclusions</h3><div>Although there was no difference in nigral iron content between both groups, higher SN iron content was associated with lower attention problems in children with ADHD and higher SN iron content was associated with better inhibitory control in NT children.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121329"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-06DOI: 10.1016/j.jad.2026.121168
Wanting Huang , Zhanzhang Wang , Hui Xia , Zhihao Guo , Hui Yan , Yuqing Li , Dewei Shang
Paroxetine exhibits significant inter-individual variability in concentrations due to nonlinear pharmacokinetics and metabolic differences, particularly at higher doses. The therapeutic reference range recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP; 20–65 μg/L) was derived primarily from studies in patients receiving 20–40 mg daily, which may not adequately reflect drug exposure at higher clinical doses. This study integrated literature data analysis and population pharmacokinetic (PPK) simulations, revealing that the mean concentration reported in the literature was 173.13 μg/L at 60 mg/d, significantly exceeding the AGNP range, while PPK simulations indicated a mean concentration of 235.94 μg/L in females at 60 mg/d, nearly twice that in males. Considering that sex and dosage significantly influence paroxetine concentrations, sex-specific exploratory therapeutic reference ranges for 60 mg/d were proposed: 85–180 μg/L for males and 150–290 μg/L for females. Based on clinical data and reported toxicity cases, a laboratory alert concentration of 350 μg/L is suggested to ensure an adequate safety margin. Overall, this study refines the paroxetine therapeutic reference range by incorporating dose- and sex-specific guidance to support more precise therapeutic drug monitoring (TDM) and promote individualized treatment, particularly at a dosage of 60 mg.
{"title":"Model-informed precision dosing of paroxetine to optimize individualized therapy in patients with mental disorders","authors":"Wanting Huang , Zhanzhang Wang , Hui Xia , Zhihao Guo , Hui Yan , Yuqing Li , Dewei Shang","doi":"10.1016/j.jad.2026.121168","DOIUrl":"10.1016/j.jad.2026.121168","url":null,"abstract":"<div><div>Paroxetine exhibits significant inter-individual variability in concentrations due to nonlinear pharmacokinetics and metabolic differences, particularly at higher doses. The therapeutic reference range recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP; 20–65 μg/L) was derived primarily from studies in patients receiving 20–40 mg daily, which may not adequately reflect drug exposure at higher clinical doses. This study integrated literature data analysis and population pharmacokinetic (PPK) simulations, revealing that the mean concentration reported in the literature was 173.13 μg/L at 60 mg/d, significantly exceeding the AGNP range, while PPK simulations indicated a mean concentration of 235.94 μg/L in females at 60 mg/d, nearly twice that in males. Considering that sex and dosage significantly influence paroxetine concentrations, sex-specific exploratory therapeutic reference ranges for 60 mg/d were proposed: 85–180 μg/L for males and 150–290 μg/L for females. Based on clinical data and reported toxicity cases, a laboratory alert concentration of 350 μg/L is suggested to ensure an adequate safety margin. Overall, this study refines the paroxetine therapeutic reference range by incorporating dose- and sex-specific guidance to support more precise therapeutic drug monitoring (TDM) and promote individualized treatment, particularly at a dosage of 60 mg.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121168"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-06-01Epub Date: 2026-02-04DOI: 10.1016/j.jad.2026.121339
Yuedong Wang , Min Zhao , Mingming Wang , Bo Xi
Background
Previous studies have established associations between perinatal parental depression and offspring depression. However, longitudinal evidence regarding the association of parental depression during offspring adolescence with offspring depression from adolescence to early adulthood remains limited.
Methods
This study utilized longitudinal data from the national China Family Panel Studies. Depressive symptoms were evaluated using the Centre for Epidemiologic Studies Depression Scale (CESD). Multivariable logistic and linear regression models with generalized estimating equations were performed.
Results
Our analysis included 2119 adolescents aged 10–17 years (47.1% female) at baseline. Over a 10-year follow-up, a 1-SD increase in maternal and paternal depressive z-scores at baseline was associated with higher risks of offspring depression (odds ratio [OR] [95% confidence interval, CI]: 1.22 [1.11, 1.35] and 1.12 [1.01, 1.23], respectively). Parental depression was associated with offspring depression: maternal depression (OR [95% CI]: 1.58 [1.24, 2.00]), paternal depression (1.41 [1.06, 1.88]), and combined parental depression (either maternal or paternal, 1.35 [1.07, 1.71]). Marginal effects analyses showed a stronger association between combined parental depression and offspring depression in males than in females (P-interaction = 0.037). Restricted cubic spline regression confirmed a linear dose-response relationship between maternal depressive scores and offspring depression risk.
Conclusions
Parental depression during offspring adolescence was associated with an increased risk of offspring depression from adolescence to early adulthood, with a linear dose-response relationship observed for maternal depressive scores. These findings underscore the intergenerational transmission of depression and suggest that parental mental health interventions may benefit both individuals and their families, potentially mitigating intergenerational effects.
{"title":"Association between parental depression during offspring adolescence and offspring depression from adolescence to early adulthood: A prospective cohort study in China","authors":"Yuedong Wang , Min Zhao , Mingming Wang , Bo Xi","doi":"10.1016/j.jad.2026.121339","DOIUrl":"10.1016/j.jad.2026.121339","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have established associations between perinatal parental depression and offspring depression. However, longitudinal evidence regarding the association of parental depression during offspring adolescence with offspring depression from adolescence to early adulthood remains limited.</div></div><div><h3>Methods</h3><div>This study utilized longitudinal data from the national China Family Panel Studies. Depressive symptoms were evaluated using the Centre for Epidemiologic Studies Depression Scale (CESD). Multivariable logistic and linear regression models with generalized estimating equations were performed.</div></div><div><h3>Results</h3><div>Our analysis included 2119 adolescents aged 10–17 years (47.1% female) at baseline. Over a 10-year follow-up, a 1-SD increase in maternal and paternal depressive z-scores at baseline was associated with higher risks of offspring depression (odds ratio [OR] [95% confidence interval, CI]: 1.22 [1.11, 1.35] and 1.12 [1.01, 1.23], respectively). Parental depression was associated with offspring depression: maternal depression (OR [95% CI]: 1.58 [1.24, 2.00]), paternal depression (1.41 [1.06, 1.88]), and combined parental depression (either maternal or paternal, 1.35 [1.07, 1.71]). Marginal effects analyses showed a stronger association between combined parental depression and offspring depression in males than in females (<em>P</em>-interaction = 0.037). Restricted cubic spline regression confirmed a linear dose-response relationship between maternal depressive scores and offspring depression risk.</div></div><div><h3>Conclusions</h3><div>Parental depression during offspring adolescence was associated with an increased risk of offspring depression from adolescence to early adulthood, with a linear dose-response relationship observed for maternal depressive scores. These findings underscore the intergenerational transmission of depression and suggest that parental mental health interventions may benefit both individuals and their families, potentially mitigating intergenerational effects.</div></div>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"402 ","pages":"Article 121339"},"PeriodicalIF":4.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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